The body has a variety of physiologic protective mechanisms to defend it against injury and disease. Inappropriate activity of some of these defenses may result in clinically evident pathologic states. We propose to study the way in which three of these important defense systems may be interrelated and some of the inhibitory mechanisms controlling their interaction. The blood enzyme systems to be investigated include the blood clotting system, the complement system and the kallikrein-kinin system. These systems play a role in thrombosis, immune reactions and in a variety of inflammatory states. Various components of these systems will be purified and the interactions between these components and plasma inhibitors studied with the view of developing ways to modify and control these important physiologic reactions. Bibliographic references: Harpel, P.C. and Cooper, N.R. 1975. Studies on Human Plasma Cl Inactivator-Enzyme Interactions. I.Mechanisms of Interaction with Cls, Plasmin and Trypsin. J. Clin. Invest. 55:593; Harpel, P.C., Hugli, T.E., and Cooper, N.R. 1975. Studies on Human Plasma Cl Inactivator-Enzyme Interactions. II. Structural Features, of an Abormal Cl Inactivator from a Kindred with Hereditary Angioneurotic Edema. J: Clin. Invest. 55: 605.